This proposal intends to use the experimental model of chronic renal insufficiency induced by 5/6 nephrectomy in the rat for the study of the effects of chronic uremia on immune responses. The following lines of investigation are projected: (a) The capacity of uremic lymphocyte to induce generalized or localized graft versus host reaction in nonuremic host will be qualitatively and quantitatively analyzed. The activity of the uremic lymphocyte in the mixed lymphocyte reaction in vitro will be studied. Finally, the response of uremic lymphocytes to stimulation with lectins (phytohemaglutinin and pokeweed mitogen) in vitro will be studied. (b) Induction of tumors by 3-methylcholanthrene will be compared in control and uremic rats. Growth of transplantable tumors in normal and uremic animals will be analyzed using isogeneic and allogeneic hosts. (c) The response of uremic rats to immunization with different antigens will be analyzed. The onset, height, and duration of the humoral response will be studied both after primary and secondary stimuli, as compared to those of control sham-operated animals. The capacity of uremic lymphocytes to restore immunologic ability of nonuremic rats rendered nonresponsive will be studied and compared to that of normal cells under similar conditions.